During the previous project period, a number of new monclonal antibodies were developed and used as probes for the study of the pathogenesis of Alzheimer's Disease. One of these antibodies, Alz- 50, appears to detect the presence of a protein, A68, which is abundant in the brains of patients with Alzheimer's Disease, but is not detectable in the normal adult brain. A68 has been detected in the cerebrospinal fluid of a small number of cases of Alzheimer's Disease. One of these antibodies, Alz-50, appears to detect the presence of a protein, A68, which is abundant in the brains of patients with Alzheimer's Disease, but is not detectable in the normal adult brain. A68 has been detected in the cerebrospinal fluid of a small number of cases of alzheimer's Disease. We have evidence that A68 is present in neurons in the developing human brain, and that it is found in neurons which die during development. In the next project period, we will attempt to test the hypothesis that the presence of A68 in cerebrospinal fluid (CSF) predicts the presence of Alzheimer pathology in the brain. Other monoclonal antibodies detect protein abnormalities in the AD brain: we will assess the potential of these for the prediction of pathologic findings. There is a possibility the patients will produce antibodies to A68: we will attempt to develop techniques for the detection in blood and CSF of such an antibody response. A68 is not present in the majority of plaques found in the brains of non- demented elderly people. We propose to conduct a comprehensive study of possible differences between both plaques and tangles in demented and non-demented elderly subject, employing monoclonal antibodies of A68 and to other proteins. We will continue our studies of the expression of A68-like immunoreactivity in the developing human central nervous system (CNS). In the cerebral cortex, the immunoreactivity is present from about 30 weeks of fetal life until about age 2 years. We have not yet examined other areas of the CNS at each stage of development. We want to extend our developmental studies to the cat brain, where there is excellent data available about the timing of cell birth, migration and cell death. Other animals, such as chick and rat, will be investigated to address specific questions relating to the possible role of A68 in cell death during development. If animal studies suggest a role for A68-like immunoreactivity in cell death, we will develop cell culture systems to examine possible changes in the cell biology of neurons on A68 expression.